Serum Free Light Chain Kinetics Is Predictive of Renal Response in Myeloma Patients With Renal Impairment-An ALLG Trial of Carfilzomib-Dexamethasone Therapy in Frontline and Relapse.

BACKGROUND AND PURPOSE: Renal impairment (RI) confers adverse prognosis in myeloma; its reversal and avoidance of dialysis are crucial. We investigated whether serum free light chain (SFLC) measurements can predict renal outcome, to enable change in therapy to optimize prognosis and avoid dialysis. PATIENTS AND METHODS: We investigated 36 myeloma patients (17 newly diagnosed [ND]; 19 relapsed refractory [RR]; with median of 5 prior lines) with eGFR 15-40 ml/min treated with carfilzomib (Cfz)-dexamethasone to determine whether SFLC kinetics can predict renal outcomes, and assess efficacy and tolerability. RESULTS: The change in involved SFLC at Cycle 2 Day 1 was significantly correlated with renal function; for every one log10 reduction in involved SFLC, eGFR increased by 9.0-15.0 mL/min at cycles 2-4, with SFLC reduction of 54%-78%. At a median follow-up of 30.6 months, renal outcomes were favorable-CRrenal 25%, MRrenal 36%. Disease responses (ND 100%, RR 75%), progression-free survival (ND 32.2 months, RR 11.1 months) and overall survival (ND not reached, RR 42.0 months) were comparable to patients without RI. There was significant toxicity, including Cfz-related cardiac impairment of 20% within a cohort with high co-morbidity, and a high incidence of infections. CONCLUSION: We propose that one log10 reduction in involved SFLC at Cycle 2 Day 1 is an appropriate target for reducing the risk of dialysis in myeloma patients with RI; below this threshold patients may benefit from a change in therapy. While Cfz-dexamethasone achieved favorable renal and disease outcomes, toxicity can be significant in this vulnerable cohort.

Real-world evaluation of persistence, effectiveness and usage patterns of tofacitinib in treatment of psoriatic arthritis in Australia.

OBJECTIVES: To describe treatment patterns and persistence of tofacitinib, interleukin 17 inhibitors (IL-17Ai) and tumour necrosis factor inhibitors (TNFi), in patients with psoriatic arthritis (PsA). METHODS: Data from adult patients with PsA and who had received at least one prescription of tofacitinib, IL-17Ai or TNFi between May 2019 and September 2021 were sourced from the Australian OPAL dataset. Persistence, analysed via Kaplan-Meier methods, and propensity score matching between tofacitinib and bDMARD (IL-17Ai and TNFi) groups were conducted. RESULTS: Of 16,692 patients with PsA, 1486 (n = 406 tofacitinib, n = 416 IL-17Ai and n = 664 TNFi) were included. More females were in the tofacitinib group (75.4%) than in the IL-17Ai (61.1%) and TNFi (64.8%) groups. Overall, 19.2% of tofacitinib patients were first line, compared with 41.8% of IL-17Ai and 62.8% of TNFi patients. In the overall population, the median persistence was 16.5 months (95% CI 13.8 to 19.5 months), 17.7 months (95% CI 15.8 to 19.6 months) and 17.2 months (95% CI 14.9 to 20.5 months) in the tofacitinib, IL-17Ai and TNFi groups, respectively. Persistence was similar in the tofacitinib/IL-17Ai matched population; however, in the tofacitinib/TNFi matched population, persistence was longer in the tofacitinib group (18.7 months, 95% CI 15.6 to 21.4 months) compared with the TNFi group (12.2 months, 95% CI 19.9 to 14.9 months). CONCLUSIONS: In this Australian real-world dataset, tofacitinib was more frequently used in later lines and among a slightly higher proportion of female patients than IL-17Ai or TNFi. Overall, treatment persistence was similar for tofacitinib, IL-17Ai and TNFi, but tofacitinib exhibited longer persistence than TNFi in a matched population. Key Points • This is the first, large real-world study from Australia investigating the demographics, treatment patterns and comparative treatment persistence of patients with psoriatic arthritis (PsA) treated with tofacitinib and biologic disease-modifying drugs (bDMARDs). • The study suggests that tofacitinib is an effective intervention in PsA with at least comparable persistence to bDMARDs: tumour necrosis factor inhibitors (TNFi) and interleukin-17 A inhibitors (IL-17Ai).

Carfilzomib, thalidomide, and dexamethasone are safe and effective in relapsed and/or refractory multiple myeloma: final report of the single-arm, multicenter, phase II ALLG MM018/AMN002 study.

This multicenter, phase II study of the Australasian Lymphoma and Leukemia Group and the Asian Myeloma Network investigated fixed-duration (18-month) treatment with carfilzomib (K), thalidomide (T), and dexamethasone (d) (KTd) in patients with relapsed and/or refractory multiple myeloma who had received one to three prior lines of therapy. Patients received induction with up to 12 28-day cycles of carfilzomib (20 mg/m2 intravenously in cycle 1 on days 1 and 2, then 56 mg/m2 [36 mg/m2 for patients ≥75 years] from day 8 onwards), thalidomide 100 mg orally in the evening and weekly dexamethasone 40 mg (20 mg for patients ≥75 years). During maintenance, thalidomide was omitted, while carfilzomib was continued on days 1, 2, 15, and 16 with fortnightly dexamethasone. The primary endpoint was progression-free survival. Secondary endpoints were overall response rate, overall survival, duration of response, safety, and tolerability. Ninety-three patients (median age 66.3 years [range, 41.9-84.5]) were enrolled and followed up for a median of 26.4 months (range, 1.6-54.6). The median progression-free survival was 22.3 months (95% confidence interval: 15.7-25.6) and the 2-year progression-free survival was 46.3% (95% confidence interval: 35.1-52.8). The median overall survival was not reached and the 2-year overall survival was 73.8% (95% confidence interval: 62.9-81.9). The overall response rate was 88% (73% had a very good partial response or better). There was no difference in the depth of response, progression-free survival or overall survival comparing Asian and non-Asian cohorts (P=0.61). The safety profile of KTd was consistent with that of each individual drug. KTd is well tolerated and effective in patients with relapsed and/or refractory multiple myeloma irrespective of Asian or non-Asian ethnicity and provides an alternative treatment option, particularly in circumstances in which the use of carfilzomib, lenalidomide, and dexamethasone (KRd) is limited by access, cost, or renal impairment.

Registry randomised trials: a methodological perspective.

Registry randomised clinical trials (RRCTs) have the potential to provide pragmatic answers to important clinical questions. RRCTs can be embedded into large population-based registries or smaller single site registries to provide timely answers at a reduced cost compared with traditional randomised controlled trials. RRCTs can take a number of forms in addition to the traditional individual-level randomised trial, including parallel group trials, platform or adaptive trials, cluster randomised trials and cluster randomised stepped-wedge trials. From an implementation perspective, initially it is advantageous to embed RRCT into well-established registries as these have typically already overcome any issues with end point validation and adjudication. With advances in data linkage and data quality, RRCTs can play an important role in answering clinical questions in a pragmatic, cost-effective way.

Attitudes of Australian breast cancer patients toward the secondary use of administrative and clinical trial data.

AIM: Little is known about the attitudes of Australian patients with a history of breast cancer toward the reuse of administrative health data and clinical trial data. Issues of consent, privacy, and information security are key to the discussion. Cancer care and research provides an opportune setting to develop an understanding of attitudes toward data sharing and reuse in individuals with a history of breast cancer. METHODS: An anonymous, online questionnaire for individuals with a history or diagnosis of breast cancer was distributed by two peak bodies (Breast Cancer Trials [BCT] and Breast Cancer Network of Australia [BCNA]) to their memberships between July 14, 2020 and October 17, 2020. Results were captured in RedCap; data analysis was undertaken using Stata, and a thematic analysis of free text responses was undertaken using NVivo. RESULTS: One hundred and thirty-two complete responses were received. Twenty-three percent of respondents had participated in a clinical trial, and 12% were currently receiving treatment (chemotherapy, radiotherapy, surgery, or endocrine). Respondents were supportive of the secondary use of de-identified administrative health data and clinical trial data, but showed concern about data security and privacy. Respondents emphasized that the reuse of data should be for improved societal health outcomes, not profit. Many assumed secondary analysis was already undertaken on de-identified administrative health data and clinical trial data. CONCLUSIONS: Respondents were supportive of the secondary use of de-identified administrative health and clinal trial data within the established bounds of good clinical practice and ethical oversight.

Pilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain.

This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-based medicine dose, maximum observed plasma concentrations of cannabinoids were dose dependant. The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-1 (0.49, 4.1), respectively). During stage II a subgroup of patients diagnosed with breast and prostate cancers with bone metastases, had the highest mean pain score improvement from baseline of 40% (unadjusted) and 33% (adjusted for rescue medication use). For all patients the most reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively, and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided acceptable bioavailability for Δ9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.

Opioid-sparing effects of ketorolac in palliative care patients receiving opioids for chronic cancer-related pain: A systematic literature review.

BACKGROUND: Standard of care in treatment of cancer-related pain involves opioids in combination with non-steroidal anti-inflammatory drugs (NSAID). Ketorolac, a NSAID, has demonstrated opioid-sparing effects in other clinical settings. AIM: This systematic literature review investigated ketorolac's opioid-sparing effects in patients receiving opioids for chronic, cancer-related pain. DESIGN: The primary outcome was total daily dose of opioids. Secondary outcomes included frequency of opioid use, use and frequency of 'rescue' medication and adverse events. Outcomes were described, and meta-analysed where possible. PROSPERO registration CRD42019130894. DATA SOURCES: Articles included original research, from any study phase or methodology, published in English in a peer-reviewed journal or conference between 1990 and 2020; included subjects >18 years; had chronic cancer-related pain and described the use of opioid-sparing effect of ketorolac. RESULTS: Nine articles were included. While there was significant heterogeneity, ketorolac may have an opioid-sparing effect, with significant reductions in total daily dose of morphine observed in a single randomised controlled trial (SMD -4.30 mg, 95% CI -5.36 to -3.25), but the changes in the before and after studies were not statistically significant -0.46 mg (95% CI -1.14 to 0.22). Ketorolac was associated with greater likelihood of complete pain relief, but the data were heterogeneous. Insufficient data were available to analyse frequency of opioid use, or rescue medication requirements. CONCLUSIONS: Given the heterogeneity of the data, adequately powered, randomised controlled trials are required to establish any opioid-sparing effect of ketorolac. For patients not responding to conventional pain management, ketorolac may have a role in treatment augmentation.

Real-world evaluation of effectiveness, persistence, and usage patterns of monotherapy and combination therapy tofacitinib in treatment of rheumatoid arthritis in Australia.

OBJECTIVE: This study aimed to describe the real-world effectiveness and treatment persistence among patients with rheumatoid arthritis treated with monotherapy and combination therapy tofacitinib and biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: This was a post hoc analysis of a retrospective, non-interventional study that extracted data for patients treated with tofacitinib or bDMARDs from the Australian OPAL dataset between March 2015 and September 2018. Monotherapy tofacitinib and bDMARDs and combination therapy tofactinib and bDMARDs were propensity score matched and treatment effectiveness and persistence of the groups were evaluated. RESULTS: In the bDMARD and tofacitinib monotherapy and combination therapy matched populations there were 1300 bDMARD initiators (n = 564 monotherapy) and 650 tofacitinib initiators (n = 282 monotherapy). In the bDMARD and tofacitinib monotherapy matched groups, 62.9% and 66.7% were in DAS-28 CRP disease remission after 18 months of treatment, respectively. In the combination therapy bDMARD and tofacitinib groups, 50% and 58.9% were in DAS-28 CRP disease remission after 18 months, respectively. The median treatment persistence was similar between the monotherapy bDMARD and tofacitinib treatment groups (36.7 months (95% CI 27.4 to "not reached') and 34.2 months (95%CI 30.3 to "not reached") respectively) as well as the combination therapy bDMARD and tofacitinib groups (32.2 months (95% CI 25.7 to 34.4) and 32.7 months (95%CI 28.7 to "not reached", respectively). CONCLUSIONS: Patients receiving combination therapy with tofacitinib or bDMARDs had higher disease activity scores at index than patients receiving monotherapy. Monotherapy with tofacitinib or bDMARDs, and combination therapy with tofacitinib or bDMARDs demonstrated similar treatment effectiveness and persistence, respectively. Key Points • This study provides real-world evidence regarding effectiveness, treatment persistence, and treatment patterns, among patients with rheumatoid arthritis (RA) treated with monotherapy or combination therapy tofacitinib. • The study suggests that monotherapy and combination therapy tofacitinib is an effective intervention in RA with persistence and effectiveness comparable to bDMARDs.

Persistence to Biologic Therapy Among Patients With Ankylosing Spondylitis: An Observational Study Using the OPAL Dataset.

OBJECTIVE: To describe the treatment response and persistence to biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with ankylosing spondylitis (AS) in a real-world Australian cohort. METHODS: This was a retrospective, noninterventional cohort study that extracted data for patients with AS from the Optimising Patient outcomes in Australian RheumatoLogy (OPAL) dataset for the period of August 2006 to September 2019. Patients were classified as either bDMARD initiators if they commenced a bDMARD during the sampling window, or bDMARD-naïve if they did not. Results were summarized descriptively. Treatment persistence was calculated using Kaplan-Meier methods. Differences in treatment persistence were explored using log-rank tests. RESULTS: There were 5048 patients with AS identified. Of these, 2597 patients initiated bDMARDs and 2451 remained bDMARD-naïve throughout the study window. Treatment with first-, second-, and third-line bDMARDs significantly reduced disease activity. Median persistence on first-line bDMARDs was 96 months (95% CI 85-109), declining to 19 months (95% CI 16-22) in second-line therapy, and 15 months (95% CI 11-18) in third-line therapy. Median persistence was longest for the golimumab (GOL) group in all lines of therapy and shortest for the etanercept (ETN) group. Differences in persistence rates according to the time period that bDMARDs were prescribed (pre- and post-2012) were also seen for ETN and adalimumab. CONCLUSION: In this cohort, all bDMARDs effectively reduced AS disease activity. Treatment persistence was sustained for up to 8 years for patients remaining on their first bDMARD, longer than on subsequent agents. Further research is needed to determine its influence on treatment recommendations.

Prevalence of sleep disturbance and the association between poor disease control in people with ankylosing spondylitis within the Australian clinical setting (ASLEEP study): a real-world observational study using the OPAL dataset.

INTRODUCTION: Sleep disturbance and fatigue are commonly reported in ankylosing spondylitis (AS) but specific prevalence and the relationship to disease control are unknown. METHOD: This retrospective non-interventional observational study of data from the OPAL dataset included patients with AS (ICD code M45, M45.0 or M08.1), aged 18 to 95 years and had completed ≥ 1 sleep questionnaire between 1 January 2019 and 30 September 2020. The prevalence of insomnia and obstructive sleep apnoea were assessed using the Insomnia Severity Index (ISI) and Multivariate Apnoea Prediction Index (MAPI), respectively. Propensity score (PS) matching based on sex, age and symptom duration increased comparability between patients administered tumour necrosis factor inhibitors (TNFi) and interleukin 17A inhibitors (IL-17Ai). RESULTS: Four hundred ninety-five patients were included. The mean ISI total score in the overall population was 8.6 ± 6.2. Self-reported moderate or severe clinical insomnia was present in 16% and 3.2% of patients, respectively. The mean MAPI score was 0.4 ± 0.3, self-reported apnoea was identified in 31.5% of patients and the mean FACIT-Fatigue score was 36.1 ± 10.7. In the PS matched population, the only treatment-related difference was the mean MAPI score (IL-17Ai 0.4 ± 0.3 and TNFi 0.3 ± 0.2, p = 0.046). Those with poor disease control (BASDAI ≥ 4) were more likely (odds ratio [OR] 7.29, 95% CI 2.37 to 22.46, p = 0.001) to have a greater severity of insomnia symptoms than those with good disease control. CONCLUSION: In this real-world AS cohort, poor disease control was associated with sleep disturbance. Little difference in sleep disturbance was observed between biologic TNFi and IL-17Ai treatment. Key Points • Sleep disturbance and fatigue are common in patients with ankylosing spondylitis. • In our real-world cohort, self-reported apnoea was reported in one-third of patients; and one in five patients reported moderate to severe insomnia. • Those with poor disease control were more likely to experience greater sleep disturbance than those with good disease control.

Treatment persistence to tolvaptan in patients with autosomal dominant polycystic kidney disease: a secondary use of data analysis of patients in the IMADJIN® dataset.

BACKGROUND: Tolvaptan is the only available disease-modifying treatment for autosomal dominant polycystic kidney disease (ADPKD). Prior to October 2020 access to tolvaptan in Australia was restricted by a controlled monitoring and distribution program called IMADJIN®. Focusing on hepatic safety, the IMADJIN® program collected real-world data on patients with ADPKD. A retrospective, secondary data analysis of the IMADJIN® dataset was undertaken to determine the time to all-cause discontinuation of tolvaptan in Australia. METHODS: Demographic and treatment data from 17 September 2018 to 30 September 2020 were extracted from the IMADJIN® dataset. Treatment persistence was analyzed using Kaplan-Meier methods, and Cox's proportional hazard models were used to analyze differences in treatment persistence by age, sex and location. RESULTS: Four hundred seventy-nine patients with ADPKD were included in the analysis. After a median follow-up of 12.0 months (95% confidence interval [CI] 2.6, 23.4), the Kaplan-Meier estimation of 12-month persistence was 76.7% (95% CI 72.2, 80.5%). 114 (23.8%) patients discontinued treatment; sex, state, and remoteness did not significantly affect treatment persistence. Patients in the youngest tertile were more likely to discontinue compared to older ages (p = 0.049). Reasons for discontinuation included: aquaretic tolerability (4.2%), hepatic adverse events (abnormal liver function tests) (2.1%), disease progression (1.5%), and acute kidney injury (0.2%). Patients with a lack of aquaretic tolerance had shorter time to discontinuation. Hepatic toxicity events were initially observed 3 months after tolvaptan initiation and were less prevalent over time. CONCLUSIONS: Persistence to tolvaptan in the real-world IMADJIN® dataset was 76%. Discontinuation due to hepatic events was low. Prescribers should take extra care when initiating treatment in younger patients as they are more likely to discontinue tolvaptan compared to older individuals. Nevertheless, the precise reason for this observation remains to be elucidated.

A pilot safety, tolerability and pharmacokinetic study of an oro-buccal administered cannabidiol-dominant anti-inflammatory formulation in healthy individuals: a randomized placebo-controlled single-blinded study.

BACKGROUND: The cannabis plant presents a complex biochemical unit of over 500 constituents of which 70 or more molecules have been classified as cannabinoids binding to cannabinoid receptors. The study aimed to investigate the safety, tolerability, and preliminary pharmacokinetics of a nanoparticle CBD formulation. METHODS: The cannabis-based medicine was elaborated with a micellular technology, to produce a water-soluble nanoparticle CBD-dominant anti-inflammatory cannabis medicine (MDCNB-02). On day one, 12 participants administered 2 sprays and on day 2 administered 6 sprays to alternating right and left cheeks [18 mg of CBD and 0.72 mg of THC]. Four other participants administered 2 and 6 sprays on days 1 and 2, respectively of a nanoparticle placebo. RESULTS: The study met the primary outcomes of safety, tolerability, and preliminary pharmacokinetics of a standardized CBD-dominant anti-inflammatory extract for oro-buccal administration. Bioavailability of a 6 mg and 18 mg dose of CBD (median IQR) was 0.87 and 8.9 ng h mL-1, respectively. The maximum concentration of CBD for the low and high doses administered once per day occurred at 60 min for both concentrations. The median half-life of the 6 mg and 18 mg CBD dose was 1.23 and 5.45 h, respectively. The apparent clearance of CBD was 115 and 34 L min-1 for a 6 mg and 18 mg dose, respectively. CONCLUSION: The oro-buccal nanoparticle formulation achieved plasma concentrations that were largely comparable to other commercial and investigated formulations relative to the concentrations administered. Moreover, there were no reports of adverse effects associated with unfavorable inflammatory sequalae.

Correction: Shrapnel, W.S.; Butcher, B.E. Sales of Sugar-Sweetened Beverages in Australia: A Trend Analysis from 1997 to 2018. Nutrients 2020, 12, 1016.

The authors wish to make the following corrections to this paper [...].

Interobserver concordance in visual assessment of Ki67 immunohistochemistry in surgical excision specimens from patients with lymph node-negative breast cancer.

PURPOSE: This study aimed to determine the interobserver concordance of two methods for proliferation assessment in breast cancer using Ki67 immunohistochemistry. METHODS: Ki67 was independently assessed in randomly selected tumour samples from patients with lymph node-negative breast cancer using two different methods: either cell counting or visual estimation of hot spot areas. For hot spot cell counting, positive and negative cell numbers were recorded for total cell counts of 300-500, 500-800 and 800-1000 cells. Visual estimation involved allocation of a score from 1 to 5 using a visual scale to estimate percentage positivity. Interobserver agreement for hot spot counting was calculated using a two-way fixed effects intraclass correlation model, and by using Cohen's kappa measure for visual assessment. Prognostic concordance between the two methods was also calculated using Cohen's kappa. RESULTS: Samples from 96 patients were included in this analysis. Interobserver agreement for hot spot cell counting was excellent (> 0.75) across all three cell count ranges, with correlation coefficients of 0.88 (95% CI 0.84-0.92), 0.87 (95% CI 0.82-0.91) and 0.89 (95% CI 0.85-0.92), respectively. Interobserver agreement with visual estimation was greatest for hot spots compared with areas of intermediate or low proliferation, with kappa scores of 0.49, 0.42 and 0.40, respectively. Both assessment methods demonstrated excellent prognostic agreement. CONCLUSIONS: Interobserver and prognostic concordance in Ki67 immunohistochemistry assessments was high using either hot spot cell counting or visual estimation, further supporting the utility and reproducibility of these cost-efficient methods to assess proliferation.

Quality of Life and Symptom Burden Improve in Patients Attending a Multidisciplinary Clinical Service for Cancer Cachexia: A Retrospective Observational Review.

BACKGROUND: Cancer cachexia negatively affects quality of life (QoL) and increases symptom burden. A multimodal treatment approach may optimize cachexia outcomes, including QoL. We evaluated QoL and symptoms over time among patients attending a multidisciplinary clinical service for cancer cachexia. METHODS: Adults with cancer who attended the clinical service three times between 2017 and 2020 were included. Quality of life and symptoms were assessed using the European Organization for Research and Treatment of Cancer Quality of life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) and the Functional Assessment Anorexia/Cachexia Therapy (FAACT) questionnaires. Physical function was assessed using the 30s sit-to-stand test and handgrip strength. RESULTS: Overall, 162 patients (age = 67.2 ± 12.0 years) were included. Mean six-month weight loss at baseline was 10.4% ± 9.4%. Mean body weight was stable between clinic visits (P = 0.904) and no change in sit-to-stand repetitions (P = 0.133) or handgrip strength (P = 0.734) occurred over time. Improvements in EORTC QLQ-C15-PAL overall QoL (Δ10.7 ± 2.5, P < 0.001), physical function (Δ8.0 ± 2.4, P = 0.003) and emotional function (Δ11.4 ± 2.9, P < 0.001) occurred by the second visit. EORTC QLQ-C15-PAL fatigue (Δ13.8 ± 2.9, P < 0.001), pain (Δ10.3 ± 3.3, P = 0.007), nausea/vomiting (Δ16.1 ± 3.0, P < 0.001) and appetite symptoms (Δ25.9 ± 3.8, P < 0.001) also improved by the second visit. FAACT total score (Δ14.6 ± 2.7, P < 0.001), anorexia-cachexia symptoms (Δ6.6 ± 1.1, P< 0.001), and physical (Δ3.7 ± 0.70, P < 0.001), emotional (Δ1.9 ± 0.60, P = 0.005) and functional wellbeing (Δ2.7 ± 0.71, P = 0.001) improved by the second visit. All improvements in EORTC QLQ-C15-PAL and FAACT outcomes were maintained at the third visit. CONCLUSION: Significant improvements in QoL and symptoms were associated with attending a cancer cachexia clinical service. Our findings support using multidisciplinary, multimodal cancer cachexia treatment approaches to improve patient wellbeing.

Impact of anti-citrullinated protein antibody on tumor necrosis factor inhibitor or abatacept response in patients with rheumatoid arthritis.

OBJECTIVE: To assess the impact of anti-citrullinated protein antibody (ACPA) serostatus on response to treatment with either tumor necrosis factor inhibitors (TNFi) or abatacept in patients with rheumatoid arthritis (RA). METHODS: Data was obtained from the Optimizing Patient outcomes in Australian RheumatoLogy (OPAL) dataset. Patient data were included in the analysis if they commenced treatment with abatacept or TNFi between 01 August 2006 and 30 June 2017 and had at least 12 months' follow-up. The primary outcome was the mean change in the clinical disease activity index (CDAI) score from baseline to 12 months. RESULTS: A total of 2,052 patients were included of which 1,415 were in the TNFi cohort (n=1,053 ACPA positive) and 637 in the abatacept cohort (n=445 ACPA positive). Patients were predominantly female (75% TNFi; 80% abatacept) with no significant difference in age between cohorts. Patients with ACPA positivity had longer disease duration before commencing treatment in both the TNFi and abatacept cohorts compared to ACPA negative patients. No difference in disease severity was observed in those with ACPA negativity compared to those with ACPA positivity. Patients treated with TNFi and abatacept had significantly improved mean change in CDAI after 12 months; ACPA positivity was associated with greater response to treatment with abatacept compared to that in patients with ACPA negativity (p=0.011). No difference in response was observed based on ACPA serostatus in patients treated with TNFi (p=0.73). CONCLUSION: Baseline ACPA positivity was associated with improved clinical response using CDAI outcome measure at 12 months for abatacept but not for TNFi therapies.

Patient literacy and awareness of medicine safety.

OBJECTIVE: To assess public understanding of medicine safety, approach to risks and preferences in accessing safety information. METHODS: Qualitative data were obtained from an online survey (n = 1079) covering four major themes around side effects and risks of medicines: willingness to accept side effects of medications, information seeking, sufficiency of information and understanding pharmacovigilance process. Comparisons were made for age, gender and social/financial status. KEY FINDINGS: Most respondents acknowledged medications were associated with side effects. If side effects were experienced, most (73%) would seek advice from their doctor or pharmacist. Four in 10 respondents felt doctors and pharmacists do not provide sufficient information about medications, even though many (47%) relied on their doctor to provide this. Although 51% felt that pharmaceutical companies were already providing enough information to patients, 95% responded that extra effort could still be made. Two-thirds of the respondents felt it was the companies' responsibility to educate doctors and pharmacists so they could pass the information on, even though younger respondents preferred direct communication to patients compared to older respondents (<24 years, 36% versus >65 years, 10%; P < 0.001). Men were more willing to accept risks, while women were more likely to seek information about their medicines. Understanding of the role of pharmaceutical companies and government in maintaining the safety of medicines was generally poor. CONCLUSIONS: There is an ongoing need for consumer education regarding medicine safety. Doctors and pharmacists remain the more trusted source of information. Pharmaceutical companies play an important role in ensuring such information is both accessible and accurate.

A Double-Blind Randomized Placebo-Controlled Study Assessing the Safety, Tolerability and Efficacy of a Herbal Medicine Containing Pycnogenol Combined with Papain and Aloe vera in the Prevention and Management of Pre-Diabetes.

Background: Herbal medicines present attractive options to patients with chronic diseases. Undertaking clinical studies with patients presenting with symptomless pre-T2D can lead to significant limitations. Methods: A 12-week randomized double-blind placebo-controlled clinical study was conducted that investigated the safety and efficacy of an herbal formulation administered orally for the treatment of pre-type 2 diabetes (pre-T2D). Results: A numerically greater proportion of subjects in the interventional arm had impaired fasting glucose (IFG) at week 12 compared to the control arm (71.0% vs. 69.0%, p = 0.75). Fewer participants had impaired glucose tolerance (IGT) at 12 weeks in the intervention arm compared to the control arm (unadjusted 58.3% vs. 66.7%, p = 0.65; adjusting for baseline IGT, p = 0.266). In a subgroup analysis, subjects with a baseline fasting plasma glucose (FPG) level in the range of 6.1-6.9 mmol/L demonstrated a non-significant lower proportion of IFG at week 12 in the intervention arm compared to the control arm (60.0% vs. 41.7% p = 0.343). Total blood cholesterol and triglyceride levels remained unchanged from baseline to week 12 in both treatment groups. Conclusions: This study suggests that a polyherbal medicine was not effective for reducing the metabolic markers associated with pre-T2D over a 12-week period. Therefore, larger studies with well-defined endpoints and of longer duration are warranted.

Sales of Sugar-Sweetened Beverages in Australia: A Trend Analysis from 1997 to 2018.

Lowering intake of sugar-sweetened beverages (SSBs) is being advocated as an obesity prevention strategy in Australia. The purpose of this study was to extend on previous reports of trends in national volume sales of SSBs. Data were extracted from commercially available datasets of beverage sales (AC Nielsen (1997-2011) and IRI Australia (2009-2018)). Linear regression was used to examine trends for the period 1997 to 2018. Per capita attribution of volume sales and sugar contribution was estimated by dividing by the Australian resident population for the relevant year. Per capita volume sales of SSBs fell 27%, from 83L/person to 61L/person, largely driven by declining sales of sugar-sweetened carbonated soft drinks (76 to 45L/person). Volume sales of non-SSB increased, from 48 to 88L/person, the largest contributor being pure unflavoured still waters (6 to 48L/person). Volume sales of non-SSBs have exceeded those of SSBs since 2015. The yearly contribution of SSBs to the sugar content of the national diet declined from 9.0 to 6.4kg/person. Major, long-term shifts are occurring in the market for non-alcoholic, water-based beverages in Australia, notably a fall in per capita volume sales of SSBs and an increase in volume sales of water. Both trends are consistent with obesity prevention strategies.